Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection
Authors: Tanayott Thaweethai, Sarah E. Jolley, Elizabeth W. Karlson, Emily B. Levitan, Bruce Levy, Grace A. McComsey, Lisa McCorkell, Girish N. Nadkarni, Sairam Parthasarathy, Upinder Singh, Tiffany A. Walker, Caitlin A. Selvaggi, Daniel J. Shinnick, Carolin C. M. Schulte, Rachel Atchley-Challenner, Leora I. Horwitz, Andrea S. Foulkes, Judith A. Aberg, Natalie L. Adolphi, Shreya Ahirwar, Shifa Ahmed, Neera Ahuja, Masanori Aikawa, Almary Akerlundh, Teresa T. Akintonwa, Aseel Al-Jadiri, Natalya Alekhina, Heather A. Algren, Akram N. Alshawabkeh, Nariman Ammar, Adit Anand, Brett R. Anderson, Lisa Aponte-Soto, Judy L. Aschner, Mary M. Atha, Andrew M. Atz, Robin L. Aupperle, Mirna Ayache, Eduardo Azziz-Baumgartner, L. C. Bailey, Fiona C. Baker, Venkataraman Balaraman, Jennifer A. Bandy, Dithi Banerjee, Deanna M. Barch, James M. Bardes, Jackson Barlocker, R. G. Barr, Arielle Baskin-Sommers, Sanjib Basu, Tracy A. Battaglia, Leah Baucom, Carmen J. Beamon, Casey L. Beaty, Noam D. Beckmann, Jasmine A. Berry, Nahid Bhadelia, Daksh Bhargava, Sultana Bhuiyan, Jiang Bian, Christian Bime, James M. Bjork, Lora J. Black, Catherine A. Blish, Jason P. Block, Amanda Bogie, Dawn Bolliger, William Bonaventura, Seuli Bose-Brill, Mary B. Bower, Andrew D. Boyd, Jerusha Boyineni, Steven B. Bradfute, Carolyn T. Bramante, M. D. Brannock, J. D. Bremner, Shari B. Brosnahan, Natalie C. Buchbinder, Elliott Bueler, Irina A. Buhimschi, Hulya Bukulmez, H. T. Bunnell, John B. Buse, Elizabeth A. Calhoun, Tingyi Cao, Michael D. Carrithers, Thomas W. Carton, Abigail Case, B.J. Casey, Faye Victoria C. Casimero, Lauren Castro, Teresa Cato, Patricia Ceger, Connie L. Cerullo, Linda Chang, Arunee A. Chang, Praneeth Chebrolu, Yong Chen, Li Qing Chen, Benjamin K. Chen, David Chestek, Robert F. Chew, Deena J. Chisolm, Dominic C. Chow, Maryanne R. Chrisant, Dimitri A. Christakis, Christopher G. Chute, Mine S. Cicek, Cheryl R. Clark, Duncan B. Clark, Geoffrey D. Clarke, Katharine N. Clouser, Thomas J. Connors, Judith A. Cook, Krista Coombs, Carlos Cordon-Cardo, Julie L. Costello, Lesley Cottrell, Kelly Cowan, Lindsay G. Cowell, Savannah Cranford, Jamie Cronin, Mollie R. Cummins, Hannah L. Curry, Viren D'Sa, Sean G. Dabney, Casey L. Daniel, Mirella Dapretto, Dawood Darbar, Paul M. Darden, Raktima Dasgupta, Soham Dasgupta, Felicia Davis Blakley, Katherine Dea, Sara J. Deakyne Davies, Lauren A. Decker, Ralph A. DeFronzo, Walter Dehority, Amelia N. Deitchman, James del Alcazar, Phoebe Del Boccio, Carlos del Rio, Marina Del Rios, Julie A. DeLisa, Sean C. Deoni, Maya Z. Diaz, John D. Dickinson, Audrey Dionne, Kathleen R. Diviak, Sarah E. Donohue, Michael J. Downey, Allen J. Dozor, Benard P. Dreyer, Kirsten B. Dummer, Matthew S. Durstenfeld, Mark S. Dworkin, Sherrie L. Edmonds, Matthew D. Elias, Jamie Elifritz, Evan Ellingworth, Amy J. Elliott, Angela M. Ellison, Mike L. Enger, Joaquin M. Espinosa, Shari Esquenazi-Karonika, Michael D. Evans, Danielle N. Evans, Julio C. Facelli, Camila S. Fang, E. Vincent S. Faustino, Maria E. Fayad Lara, Candace H. Feldman, Alexander G. Fiks, Rebecca Fineman, Aloke V. Finn, Melinda S. Fischer, Megan L. Fitzgerald, Valerie J. Flaherman, Thomas J. Flotte, Daniel Forsha, Meghan R. Fortune, John J. Foxe, Nicole Franks, Michael B. Freedman, Catherine E. Freeland, Naomi P. Friedman, Greta Fry, Margot Gage Witvliet, Emily J. Gallagher, Richard Gallagher, Hugh Garavan, Sunanda M. Gaur, Dylan G. Gee, Maria Laura Gennaro, Lynn B. Gerald, Saikat B. Ghosh, Joseph T. Giacino, Andrew T. Girvin, Stephanie L. Godfrey, Mark P. Goldberg, Steven N. Goodman, Howard S. Gordon, Ramkiran Gouripeddi, Paige Graham, Joey P. Granger, Kevin M. Gray, Tina Greimes, Rachel S. Gross, Nicholas Guthe, Evan Gutter, Stephanie Haasnoot, Emily C. Hadley, Melissa A. Haendel, Stephanie Hafner, Katia C. Halabi, Patrick C. Hanley, Ashraf S. Harahsheh, Michelle S. Harkins, Kimberly L. Hartwig, Keren Hasbani, Sharon Hasek, Kristine S. Hauser, Andrew C. Heath, Camden L. Hebson, Mary M. Heitzeg, Monica Hendrickson, Timothy J. Henrich, Alfonso C. Hernandez-Romieu, Christina M. Hester, Miranda Higginbotham, Sophia Hill, Kathryn Hirabayashi, On Ho, Laura Hobart-Porter, M. C. Hoffman, Maryann Holtcamp, Travis K. Hong, Benjamin D. Horne, Carol R. Horowitz, Daniel S. Hsia, Harvey Hsu, Priscilla Y. Hsue, Matthew Huentelman, Bryan E. Huerta, Jared D. Huling, Kathy Hummel, William G. Iacono, Alejandra L. Ibanez, Carmel Ibeawuchi, Katherine Irby, Nahed Ismail, Joanna Jacobus, Vanessa L. Jacoby, Leonard A. Jason, Vidhi Javia, Kyle J. Jennette, Terry L. Jernigan, Sihang Jiang, Naimin Jing, Jace D. Johnny, Nadia Johnson, Brandi Johnson, Brandon Johnson, Pei-Ni Jone, Suzanne E. Judd, Joy J. Juskowich, Edmond K. Kabagambe, David C. Kaelber, Diane G. Kanjilal, Mayank M. Kansal, Tyler J. Kasmarcak, Daniel Kaufman, Rika Kawakami, Dean L. Kellogg, Denise A. Kent, Deepshikha Kewlani, Dhruv Khullar, Keri S. Kim, Arthur Y. Kim, Patricia A. Kinser, Lawrence C. Kleinman, Elizabeth B. Klerman, Matthew J. Kluko, Stacey Knight, Misaki Kobayashi, Karla J. Kopp, Michael Koropsak, Jessica S. Kosut, Ellen Kraig, Amanda Krausert, Ana C. Krieger, Hema Krishna, Aparna Krishnamoorthy, Sankaran S. Krishnan, James P. Lahs, Angela R. Laird, Victoria Laleau, Michelle F. Lamendola-Essel, Jeremy Landeo-Gutierrez, Sean M. Lang, Christine L. Larson, James P. Lash, Jessica Lasky-Su, Gregory Laynor, Simon Lee, Grace M. Lee, F. E. Lee, Matthew A. Lee, Peter J. Leese, R. C. Lefebvre, Angelica J. Levreault, Kennedy C. Lewis, Lu Li, Peter Paul C. Lim, Janet Y. Lin, Krista M. Lisdahl, Matthew B. Litvack, Xiaokang Liu, Jennifer Lloyd, Jennifer K. Logue, Johanna J. Loomba, Vitaly Lorman, Yiwen Lu, Katelyn R. Ludwig, Allison M. Lutz, Jeri Mack, Abeer M. Mahmoud, Cheryl L. Maier, Shahdi K. Malakooti, Sergey Malchenko, Gail L. Mallett, Gabrielle Maranga, Megan W. Martel, Susanne P. Martin-Herz, Maria Martinez-Lage, Christine Maughan, Cammeo Mauntel-Medici, Heidi T. May, Kenneth H. Mayer, Diego R. Mazzotti, Caitryn M. McCallum, Brian W. McCrindle, Russell J. McCulloh, Dylan McDonald, Stephanie McInnis, Julie A. McMurry, Asuncion Mejias, Jonathan Melamed, Martha Menchaca, Alan L. Mendelsohn, Lucio Miele, Mitchell G. Miglis, Cris Milne, Joshua D. Milner, Roger A. Mitchell, Murray A. Mittleman, Sindhu Mohandas, Jonathan G. Monteiro, Vanessa Monzon, David J. Moreno, Lerraughn M. Morgan, Dmitry Morozyuk, Keith E. Morse, Erick Moyneur, Praveen C. Mudumbi, Eva M. Müller-Oehring, Naoko Muramatsu, Hugh Musick, Kshema Nagavedu, Erica R. Nahin, Anoop M. Nambiar, Benjamin H. Natelson, Michael C. Neale, Manette Ness-Cochinwala, Jane W. Newburger, Lisa T. Newman, Amber N. Nguyen, Lauren Nichols, Sheila M. Nolan, Seth Noland, Richard M. Novak, George T. O'Connor, John J. O'Keefe, Princess U. Ogbogu, Carlos R. Oliveira, Matthew E. Oster, Robert F. Padera, Henry H. Paik, Nathan M. Pajor, Huaqin Helen Pan, Deepti Pant, Andrew Partridge, Payal B. Patel, Saaya Patel, Khushboo Patel, Martin P. Paulus, Ronald M. Payne, Ann Pearman, Myriam Peralta-Carcelen, Nicolas L. Perez, Emily R. Pfaff, De-Ann M. Pillers, Chloe E. Pitsch, Neil H. Pliskin, Michael A. Portman, Radu Postelnicu, Jennifer S. Potter, Bellur S. Prabhakar, Priya Prahalad, Bharati Prasad, Barbara Predki, Alexander J. Preiss, Heather M. Prendergast, Davin K. Quinn, Yuri Quintana, Dustin J. Rabideau, Jonathan M. Radosta, Jeffrey Radwell, Hengameh Raissy, Ramaswamy Ramchandran, Isabelle Randall, Suchitra Rao, Amy Rapkiewicz, Sonja A. Rasmussen, Hanieh Razzaghi, Candida J. Rebello, Paulina A. Rebolledo, Neha V. Reddy, Unma M. Reddy, Cara Reedy, Jalees Rehman, R. R. Reichard, Kayleigh M. Reid, Jane E. Reusch, Kyung E. Rhee, Mary B. Rice, John-Ross R. Rizzo, Nadia R. Roan, Polly Robarts, Timothy R. Roberts, Nitza Rochez, Kathleen E. Rodgers, Colin M. Rogerson, Maria E. Romero, Johana M. Rosas, Erika B. Rosenzweig, Russell L. Rothman, Nadine G. Rouphael, Mark W. Russell, Melissa Rutherfoord, Arash A. Sabati, Samer B. Sader, Marzieh Salehi, Amy L. Salisbury, Barbara A. Sampson, Yamuna Sanil, Alice I. Sato, Sharon H. Saydah, Michael S. Schechter, Edward J. Schenck, Katherine I. Schlepphorst, Julia Schuchard, Tina L. Schuh, Jennifer A. Sculley, Alan C. Seifert, Anisha K. Sekar, Rangaraj Selvarangan, Sudha Seshadri, Howard D. Sesso, Dimpy P. Shah, Divya Shakti, Nancy L. Shapiro, Suchetha Sharma, Kumar Sharma, Shubhi Sharma, Kavita Sharma, Gwendolyn Shaw, Eyal Shemesh, Yishan Shen, Elizabeth Shenkman, Stephanie Shiau, Michelle Siciliano, Aylin Simsir, Veronica E. Smith, Jessica N. Snowden, Isaac H. Solomon, Leslie A. Spikes, Lindsay M. Squeglia, Shubhika Srivastava, Mary L. St. Jean, Kenneth A. Stapleford, Cheryl R. Stein, Michelle D. Stevenson, Sarah A. Stewart de Ramirez, Lauren E. Stiles, Aryeh Stock, Melissa S. Stockwell, James R. Stone, Jeran Stratford, Til Stürmer, Vignesh Subbian, Jun Sun, Mehul S. Suthar, Ashley Sylvera, David M. Systrom, Jacqueline Szmuszkovicz, Maria M. Talavera-Barber, Kelan G. Tantisira, Nancy Tartt, Tracy Terlinde, Ronald J. Teufel, Deepika Thacker, Mansi Thakrar, Stephen N. Thibodeau, Gelise L. Thomas, Moriah E. Thomason, Jiayi Tong, Robert Torres, Jessica Traenkner, Robin Tragus, Joel D. Trinity, Jena S. Tronieri, Andrea B. Troxel, Jennifer Truong, Dongngan T. Truong, Joel Tsevat, Mmekom M. Udosen, Kristen Unterberger, Paul J. Utz, Viola Vaccarino, Brittany B. Vallejos, Terry L. Vanden Hoek, Nita Vangeepuram, Jay K. Varma, Suzanne D. Vernon, Crystal M. Vidal, Sara Vivensi, Adam S. Vohra, Laura K. Wagner, Fei Wang, David Warburton, Megan R. Warner, Rebecca L. Watkins, Sara E. Watson, Ryan Webb, Ryan M. Weeks, Mark G. Weiner, Alan Werzberger, Shelby C. West, Jordan C. Weyer, Jennifer L. Wheeler, Kenneth J. Wilkins, Natasha J. Williams, Charles T. Williams, Erika S. Wimberly, Terra J. Winter, Scott C. Woller, Rachel Wong, Jeremy P. Wood, John C. Wood, Marion J. J. Wood, Qiong Wu, Yinglin Xia, Jie Xu, Samuel Yang, H. S. Yin, Hsiang S. Yin, Yun Jae Yoo, Chloe E. Young, Natalie M. Young, Chengxi Zang, William T. Zempsky, Bingyu Zhang, Yongkang Zhang, Dazheng Zhang, Emily Zimmerman, John Andrefsky, Jeanne M Marrazzo, Jennifer Dixon, Lisa Gale, Phoebe Maholovich, Praveen Sudhindra, Tiffany Thompson, Elyce Sheehan, Alisha Parada, Kiirk Knowlton, Jeffrey L. Anderson, Marjorie McIntyre, Sean McCandless, Sarah Montoya, Debra Davis, Eric Spanier, Thomas Wodushek, Ron Sokol, Yvonne Maldonado, Karen Jacobson, Xiaolin "Kathleen" Jia, Jake Scott, Orlando Quintero, Francois Haddad, Hannah Valantine, Roham Zamanian, Divya Pathak, Jeanette Boyce, Francesca Facco, Sarah Hankle, John A. Vargo, Donna Campbell, Donna Armstrong, Madison Mann, Nicole Burrell, Anna Bartholomew, William A. Grobman, Barbara Cackovic, Baylee Klopfenstein, Samantha Weigand, E. Kaye Snow, Kathleen Fennig, M. Sean Esplin, Denise Lamb, Amanda Nelsen, Jocelyn Phipers, Lauren Fischer, Olivia Docter, Jeanette Brown, Angelica DeMartino, Donna Allard, Emily Miller, Sabine Z. Bousleiman, Megan M. Loffredo, Ashley Vanneman, Imene Beche, Rosalyn Chan-Akeley, Luis D. Pacheco, Jennfier D. DeVolder, Ashley Salazar, Lisa Thibodeaux, Jennifer Cornwell, Amelia A. Nounes, Eugenia Sweet, Abigail Pierse, Brittany Desantis, Parmjit Gill-Jones, David N. Hackney, Suneet P. Chauhan, Felecia Ortiz, Jenifer Treadway, Juanita Rugerio, Kelly Clark, Molly Leatherland, Sally Timlin, Chelsea Grinnan, Jennifer Ferrara, Michelle Kominiarek, Dequana Jones, Trista Reynolds, Katherine M Kearns, Eleanor Saffian, Mariana Karasti, Chrsitinia Pizzi, Anna Filipczak, Emily Long, Megan Mitchell, Katia J. Barrett, Celia Mullowney, George A. Macones, George A. Alba, Radica Alicic, Natasha Altman, Khamal Anglin, Urania Argueta, Hassan Ashktorab, Gaston Baslet, Ingrid V. Bassett, Lucinda Bateman, Brahmchetna Bedi, Shamik Bhattacharyya, Marie-Abele Bind, Andra L. Blomkalns, Hector Bonilla, Hassan Brim, Patricia A. Bush, Mario Castro, James Chan, Alexander W. Charney, Peter Chen, Lori B. Chibnik, Helen Y. Chu, Rebecca G. Clifton, Maged M. Costantine, Sushma K. Cribbs, Sylvia I. Davila Nieves, Steven G. Deeks, Alexandria Duven, Ivette F. Emery, Nathan Erdmann, Kristine M. Erlandson, Kacey C. Ernst, Rachael Farah-Abraham, Cheryl E. Farner, Elen M. Feuerriegel, Judes Fleurimont, Vivian Fonseca, Nicholas Franko, Vivian Gainer, Jennifer C. Gander, Edward M. Gardner, Linda N. Geng, Kelly S. Gibson, Minjoung Go, Jason D. Goldman, Halle Grebe, Frank L. Greenway, Mounira Habli, John Hafner, Jenny E. Han, Keith A. Hanson, James Heath, Carla Hernandez, Rachel Hess, Sally L. Hodder, Matthew K. Hoffman, Susan E. Hoover, Beatrice Huang, Brenna L. Hughes, Prasanna Jagannathan, Janice John, Michael R. Jordan, Stuart D. Katz, Elizabeth S. Kaufman, John D. Kelly, Sara W. Kelly, Megan M. Kemp, John P. Kirwan, Jonathan D. Klein, Kenneth S. Knox, Jerry A. Krishnan, Andre Kumar, Adeyinka O. Laiyemo, Allison A. Lambert, Margaret Lanca, Joyce K. Lee-Iannotti, Brian P. Logarbo, Michele T. Longo, Carlos A. Luciano, Karen Lutrick, Jason H. Maley, Gail Mallett, Jai G. Marathe, Vincent Marconi, Gailen D. Marshall, Christopher F. Martin, Yuri Matusov, Alem Mehari, Hector Mendez-Figueroa, Robin Mermelstein, Torri D. Metz, Richard Morse, Jarrod Mosier, Christian Mouchati, Janet Mullington, Shawn N. Murphy, Robert B. Neuman, Janko Z. Nikolich, Ighovwerha Ofotokun, Elizabeth Ojemakinde, Anna Palatnik, Kristy Palomares, Tanyalak Parimon, Samuel Parry, Jan E. Patterson, Thomas F. Patterson, Rachel E. Patzer, Michael J. Peluso, Priscilla Pemu, Christian M. Pettker, Beth A. Plunkett, Kristen Pogreba-Brown, Athena Poppas, John G. Quigley, Uma Reddy, Rebecca Reece, Harrison Reeder, W. B. Reeves, Eric M. Reiman, Franz Rischard, Jonathan Rosand, Dwight J. Rouse, Adam Ruff, George Saade, Grecio J. Sandoval, Jorge L. Santana, Shannon M. Schlater, Frank C. Sciurba, Fitzgerald Shepherd, Zaki A. Sherif, Hyagriv Simhan, Nora G. Singer, Daniel W. Skupski, Amber Sowles, Jeffrey A. Sparks, Fatima I. Sukhera, Barbara S. Taylor, Larissa Teunis, Robert J. Thomas, John M. Thorp, Paul Thuluvath, Amberly Ticotsky, Alan T. Tita, Katherine R. Tuttle, Alfredo E. Urdaneta, Daisy Valdivieso, Timothy M. VanWagoner, Andrew Vasey, Monica Verduzco-Gutierrez, Zachary S. Wallace, Honorine D. Ward, David E. Warren, Steven J. Weiner, Shelley Welch, Sidney W. Whiteheart, Zanthia Wiley, Juan P. Wisnivesky, Lynn M. Yee, Sokratis Zisis
Journal: JAMA (2023)

Importance SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID . Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure SARS-CoV-2 infection. Main Outcomes and Measures PASC and 44 participant-reported symptoms (with severity thresholds). Results A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. Conclusions and Relevance A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.